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Development of a new drug for endometrial carcinoma targeting cycylin A

Research Project

Project/Area Number 25293340
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionShinshu University

Principal Investigator

SHIOZAWA Tanri  信州大学, 学術研究院医学系, 教授 (20235493)

Co-Investigator(Kenkyū-buntansha) SUZUKI Akihisa  信州大学, 医学部附属病院, 特任研究員 (10547095)
ASAKA Ryoichi  信州大学, 医学部附属病院, 助教 (00623688)
ANDO Hirofumi  信州大学, 医学部附属病院, 助教 (80722925)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2013: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords子宮内膜癌 / サイクリンA / 分子標的薬 / 低分子化合物 / prohibitin
Outline of Final Research Achievements

Since the number of endometrial carcinoma (EC) patients is sharply increasing in Japan, development of new therapeutic strategies is mandatory. We previously found the increased expression of cyclin A, a cell-cycle regulatory molecule, to be correlated with poor prognosis of EC patients. Therefore, we considered cyclin A to be a important therapeutic target. After screening of a library containing more than 10,000 low molecular weight compound, we found that a molecule with 300 Da (termed “X” ) had strongly suppressed the transcription of cyclin A and growth of EC xenografts on mice, suggesting “X” to be a promising lead compound. In order to improve the function of “X”, we examined the working mechanism of “X”, and found X to bind to a transcriptional factor, prohibitin. Thus, prohibitin-oriented structural modification seems to pave the way for a new drug development.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (13 results)

All 2015 2014 2013 Other

All Journal Article (9 results) (of which Peer Reviewed: 6 results) Presentation (4 results)

  • [Journal Article] 4-hydroxy estrogen induces DNA damage on codon 130/131 of PTEN in endometrial carcinoma cells2015

    • Author(s)
      Ke H, Suzuki A, Miyamoto T, Kashima H, Shiozawa T
    • Journal Title

      Mol Cell Endocrinol

      Volume: 400 Pages: 71-7

    • DOI

      10.1016/j.mce.2014.10.027

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Recurrent low-grade endometrial stromal sarcoma with intracaval and intracardiac tumor thrombus: diagnosis, treatment, and surgical management2014

    • Author(s)
      Miyamoto T, Tachibana R, Kobara H, Takano T, Kato H, Shimizu A, Ohya A, Uehara T, Shiozawa T.
    • Journal Title

      International Cancer Conference Journal

      Volume: 3 Issue: 1 Pages: 1-7

    • DOI

      10.1007/s13691-013-0134-6

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Morphological alterations in protamine-deficient spermatozoa2014

    • Author(s)
      Utsuno H, Miyamoto T, Oka K, Shiozawa T
    • Journal Title

      Hum Reprod

      Volume: 29 Issue: 11 Pages: 2374-81

    • DOI

      10.1093/humrep/deu225

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polypoid endometriosis of the ovary mimicking ovarian carcinoma dissemination: a case report and literature review2014

    • Author(s)
      4.Yamada Y, Miyamoto T, Horiuchi A, Ohya A, Shiozawa T
    • Journal Title

      J Obstet Gynaecol Res

      Volume: 40 Issue: 5 Pages: 1426-30

    • DOI

      10.1111/jog.12358

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clonality analysis suggests that STK11 gene mutations are involved in progression of lobular endocervical glandular hyperplasia (LEGH) to minimal deviation adenocarcinoma (MDA).2013

    • Author(s)
      Takatsu A, Miyamoto T, Fuseya C, Suzuki A, Kashima H, Horiuchi A, Ishii K, Shiozawa T
    • Journal Title

      Virchows Arch

      Volume: 462(6) Issue: 6 Pages: 645-51

    • DOI

      10.1007/s00428-013-1417-1

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Lipocalin2 enhances the matrix metalloproteinase-9 activity and invasion of extravillous trophoblasts under hypoxia.2013

    • Author(s)
      Kobara H, Miyamoto T, Suzuki A, Asaka R, Yamada Y, Ishikawa K, Kikuchi N, Ohira S, Shiozawa T.
    • Journal Title

      Placenta

      Volume: 34(11) Issue: 11 Pages: 1036-43

    • DOI

      10.1016/j.placenta.2013.08.004

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Immunohistochemical expression of core 2 β1,6-N-acetylglucosaminyl transferase 1 (C2GnT1) in endometrioid-type endometrial carcinoma: a novel potential prognostic factor.2013

    • Author(s)
      Miyamoto T
    • Journal Title

      Histopathology

      Volume: Feb 9 [Epub ahead of print] Issue: 7 Pages: 986-93

    • DOI

      10.1111/his.12107

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 進行子宮頸がんの根治手術 : 術前化学療法後の広汎子宮全摘 (今月の臨床 進行婦人科がんの集学的治療) -- (子宮頸がん)2013

    • Author(s)
      宮本 強 , 塩沢 丹里
    • Journal Title

      臨床婦人科産科

      Volume: 67(11) Pages: 1099-1104

    • NAID

      40019860821

    • Related Report
      2013 Annual Research Report
  • [Journal Article] 月経異常患者の子宮体がん予防 (今月の臨床 婦人科がんの予防戦略と早期診断) -- (子宮体がん)2013

    • Author(s)
      宮本 強 , 塩沢 丹里
    • Journal Title

      臨床婦人科産科

      Volume: 67(8) Pages: 805-812

    • NAID

      40019775961

    • Related Report
      2013 Annual Research Report
  • [Presentation] 卵巣明細胞癌発生に関与する新規候補遺伝子の機能的スクリーニング2013

    • Author(s)
      安藤大史、宮本 強、山田 靖、鈴木昭久、浅香亮一、石川香織、小原久典、塩沢丹里
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
  • [Presentation] Identification of novel genes involved in clear cell carcinogenesis of the overy using retrovirus-based cDNA expression library

    • Author(s)
      Shiozawa T,Miyamoto T,Suzuki A,Asaka R.
    • Organizer
      American Assosiation for Cancer Research Annual Meeting 2013
    • Place of Presentation
      ワシントンD.C(アメリカ)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 1.子宮頸部嚢胞性病変の取り扱い2.子宮内膜癌の発生とエストロゲン

    • Author(s)
      塩沢丹里
    • Organizer
      第21回鴨和腫瘍カンファレンス
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] 1.子宮頸部嚢胞性病変の取り扱い2.子宮内膜癌の発生とエストロゲン

    • Author(s)
      塩沢丹里
    • Organizer
      第23回熊本女性医学講座
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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